DESCRIPTION: The broad long-term objectives of this research are 1.) to describe the normal aging-related changes of the lens plasma membrane-associated cytoskeleton in rats 2.) to describe alterations of the normal dynamics of the lens plasma membrane-associated cytoskeleton which occur as a consequence of selenite-induced cataract. The specific objectives of this proposal will be to isolate from rat lenses distinct membrane fractions which probably represent different domains of the lens plasma membrane. Each of these fractions contains its own characteristic set of cytoskeletal proteins or fragments of cytoskeletal proteins which reflect the dynamic changes in the membrane-associated cytoskeleton associated with that particular membrane fraction or domain. In other species, specific changes in cytoskeletal elements are part of normal lens differentiation, maturation and aging. Interference with these changes is associated with cataract. It is currently unknown how these cytoskeletal elements interact with the lens plasma membrane, or special domains of the lens plasma membrane. Four distinct plasma membrane fractions will be isolated from the rat lenses , and using electrophoresis and immunochemical methods, specific cytoskeletal peptides will be identified and quantitated in each different membrane fraction. The same methods will be used to examine how the normal aging related changes in the rat lens plasma membrane-associated cytoskeleton are altered during the formation of cataracts, using a rat lens cataract model which shares many important biochemical features with human senile cataract. The research will provide basic information on the composition and againg-related dynamics of the lens plasma membrane-associated cytoskeleton. Also, these studies will describe changes in the dynamic cytoskeletal network which are associate with the formation of cataracts. It is anticipated this inforamtion will be useful in the understanidng of human senile cataract.